Pharmaceutical companies in the UK need to think carefully about whether their clinical trials are “fit for purpose” at a time of unprecedented change in the structures and priorities of the National Health Service, a consultant with long experience in the industry has warned.

The evidence, said Alan Jones, managing consultant for ajc Healthcare, was that the National Institute of Health and Clinical Excellence had now produced more than 120 Technology Appraisal Guidances and over 40 Clinical Practice Guidelines for England and Wales. Yet only 33% of these had recommended the drug or procedure for routine use. NICE’s counterpart, the Scottish Medicines Consortium, had assessed more than 200 technologies and rejected 25% of these outright.

In fact, Jones noted at the recent 28th Annual Conference of the Institute of Clinical Research in Birmingham, the NHS was so “fed up” with new drugs falling short of its requirements for cost-effectiveness that it had commissioned its own Phase IV trials – through the National Institute for Health Research’s Health Technology Assessment programme – to answer the questions it was asking of manufacturers.

The Ministerial Industry Strategy Group had reached a similar conclusion in its recently published Long-Term Leadership Strategy for the pharmaceutical industry. It found that clinical trials “deliver the data needed for regulatory approval, but tend to not provide the overall health outcome and economic data that NICE needs; nor do they give a real indication as to the experiences patients will have when taking the medicine in an uncontrolled environment, on either the safety or effectiveness of the medicine”.

Data types sought are changing

Not only were the types of data sought by NICE and the NHS changing, but clinical trials also needed to take into account the most radical reform programme in the UK health service since its post-war foundation. These reforms were producing new ranks of payers for approved medicines as well as new opportunities for targeted studies that reflected government health targets or the devolution of care, Jones pointed out.

Did industry fully understand, for example, the implications of practice-based commissioning, ‘payment by results’, nurse and pharmacist prescribing, the emphasis on management of long-term conditions, the ‘reconfiguration’ of hospitals to move less specialised care out into community-based general practice, or the shift towards ‘joined-up’ care involving health and social services, he asked.

This “huge turbulence” in the NHS was also an incentive to conduct trials in different locations, different patients, with different healthcare professionals (e.g., prescribing nurses and pharmacists) or with different outcomes. One example, Jones noted, was that the annual health checks now used by the Healthcare Commission to assess and rate the performance of local NHS organisations included improved health outcomes for people with long-term conditions. Clinical trials could be redesigned to meet those needs by, say, demonstrating a reduction in emergency admissions, he suggested.

Payer power

In terms of payer power, most of the action in England centred on the consolidated network of 152 Primary Care Trusts (PCTs), with new Clinical Executives coming on board and a remit to pursue ‘intelligent’ commissioning of goods and services that made better use of local health data. Moreover, commissioning and health technology assessment now went “hand in hand”. What these payers wanted, Jones told the conference, was pragmatic, realistic clinical and cost-effectiveness data with local relevance.

There were indications, though, that pharmaceutical companies had failed to grasp the extent of the need to integrate payer priorities into clinical development. Lack of economic data was the most common reason for drugs being rejected by the SMC, Jones noted. Moreover, payers were more and more challenging the relevance of biomarkers and other endpoints used by the pharmaceutical industry to demonstrate effectiveness. Outcomes and epidemiological data were taking increasing precedence.

The new paradigm, Jones said, was that drug registration was just “the end of the beginning”. He encouraged clinical researchers and industry to “get out more” and talk to their new customers in the NHS. They should also pay close attention to recent government initiatives in this area, such as the NHS R&D strategy, ‘Best Research for Best Health’ (“your bible”), and the Cooksey review, which recommended earlier involvement of NICE and the SMC in the clinical development process to define targets.

With the balance of power shifting to the payers and the assessors, the NHS increasingly would “not allow you to do clinical trials in their patients unless they say so”, Jones warned.